The National Institute on Aging has awarded a $2.4 million, five-year grant to the New York University (NYU) College of Dentistry to explore age-related, chronic low-grade inflammation and changes in the gut microbiome.
Chronic low-grade inflammation that develops with age, known as inflammaging, plays a key role in the rate of aging and age-related conditions such as diabetes and heart disease. It is likely the result of a dysfunctional relationship between an imbalanced gut microbiome and the immune system, NYU Dentistry said.
Xin Li, PhD, associate professor of molecular pathobiology at NYU Dentistry and the project’s contact principal investigator, studies metabolites, which are small molecules produced during metabolism, and how they function as signals in aging and other conditions.
Li and her colleagues recently found that the elevation of a metabolite called succinate is associated with aging in both humans and mice. Elevated levels of succinate alter the gut microbiome by increasing the abundance of disease-causing organisms. They also activate the succinate receptor to increase inflammation and the production of myeloid lineage in the bone marrow.
Preliminary data from Li’s team shows that the interplay among gut microbes, altered metabolites, and the activation of succinate receptor contributes to inflammaging.
The researchers next will examine the impact of succinate elevation on the gut microbiome in animal models and how these changes regulate signaling to promote inflammation. Then, they will “reprogram” the microbiome using antibiotics and fecal transplants to see if it alters the inflammation. The researchers additionally will study the role of bone marrow in succinate-stimulated inflammation and the myeloid lineage shift.
“Our study aims to help us better understand how the aging microbiome relates to the causes and pathophysiology of age-related chronic inflammation,” said Li. “If we find that targeting the gut microbiome and succinate receptor activation can alleviate inflammaging, this could provide us with novel targets for treating age-related inflammation.”
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